We will study incidence, prevalence and survival from stroke in Rochester, MN, 1980-84, and will study trends in presence and management of hypertension as a stroke risk factor. We will do a blood pressure survey in Rochester to determine the pool of uncontrolled hypertension. We will study the relationship of carotid atherosclerosis to cigarette smoking and to serum apolipoprotein A-I. We will study embolic cerebral infarction and trends in presence and management of cardiac disorders as risk factors for stroke in a defined population. We plan a controlled clinical trial of medical vs surgical treatment of asymptomatic carotid stenosis. We will examine the role of neuropeptides and prostaglandins on the local regulation of cortical vasomotor tone and CBF by identifying distribution of VIP, CCK, and SP in the perivascular plexi; correlating release of these peptides and several prostanoids from cortical terminals with changes in CBF; comparing the pharmacology of the effects of focal stimulation and exogenously applied agents on CBF. We will study the role of prostanoids on subarachnoid hemorrhage-induced vasospasm, and the effects of exercise on CBF in man. We will delineate regional, biochemical and subcellular vulnerabilities of gerbil brains to cerebral ischemia by using global and regional cerebral ischemia and by using immunohistochemical, immunoelectron microscopic, autoradiographic and enzyme-histochemical methods combined with measurement of regional CBF, ATP and other nucleotides and polyunsaturated fatty acid, and with exploration of mitochondrial respiratory function, adenylate cyclase system and membrane protein phosphorylation. The mechanism of slowly progressive cerebral ischemia will be investigated with a newly developed experimental model (rabbit) by using immunohistochemical, and electron microscopic methods combined with measurement of regional CBF, ATP and other nucleotides, NMR parameters (T - and T -relaxation time), electrolyte and water contents, polyunsaturated fatty acids and mitochondrial respiratory function.